NMR solution structure of the neurotrypsin Kringle domain.
Neurotrypsin is a multidomain protein that serves as a brain-specific serine protease. Here we report the NMR structure of its kringle domain, NT/K. The data analysis was performed with the BACUS (Bayesian analysis of coupled unassigned spins) algorithm. This study presents the first application of BACUS to the structure determination of a 13C unenriched protein for which no prior experimental 3D structure was available. NT/K adopts the kringle fold, consisting of an antiparallel beta-sheet bridged by an overlapping pair of disulfides. The structure reveals the presence of a surface-exposed left-handed polyproline II helix that is closely packed to the core beta-structure. This feature distinguishes NT/K from other members of the kringle fold and points toward a novel functional role for a kringle domain. Functional divergence among kringle domains is discussed on the basis of their surface and electrostatic characteristics.
Ozhogina
Olga A
OA
Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. oao.sputnik@gmail.com
Grishaev
Alexander
A
Bominaar
Emile L
EL
Patthy
László
L
Trexler
Maria
M
Llinás
Miguel
M
D000595:Amino Acid Sequence; D000818:Animals; D001499:Bayes Theorem; D018082:Kringles; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry*; D012996:Solutions
D012996:Solutions; D012697:Serine Endopeptidases; C108493:neurotrypsin